Outcome and Biomarker Supervised Deep Learning for Survival Prediction in Two Multicenter Breast Cancer Series.

backgroundPrediction of clinical outcomes for individual cancer patients is an important step in the disease diagnosis and subsequently guides the treatment and patient counseling. In this work, we develop and evaluate a joint outcome and biomarker supervised (estrogen receptor expression and MATERIALS AND

methodsUsing deep learning, we trained convolutional neural networks (CNNs) with digitized tissue microarray (TMA) samples of primary hematoxylin-eosin-stained breast cancer specimens from 693 patients in the FinProg series as input and breast cancer-specific survival as the endpoint. The trained algorithms were tested on 354 TMA patient samples in the same series. An independent set of whole-slide (WS) tumor samples from 674 patients in another multicenter study (FinHer) was used to validate and verify the generalization of the outcome prediction based on CNN models by Cox survival regression and concordance index (c-index). Visual cancer tissue characterization, i.e., number of mitoses, tubules, nuclear pleomorphism, tumor-infiltrating lymphocytes, and necrosis was performed on TMA samples in the FinProg test set by a pathologist and combined with deep learning-based outcome prediction in a multitask algorithm.

resultsThe multitask algorithm achieved a hazard ratio (HR) of 2.0 (95% confidence interval [CI] 1.30-3.00),

conclusionsA multitask deep learning algorithm supervised by both patient outcome and biomarker status learned features in basic tissue morphology predictive of survival in a nationwide, multicenter series of patients with breast cancer. The algorithms generalized to another independent multicenter patient series and whole-slide breast cancer samples and provide prognostic information complementary to that of a comprehensive series of established prognostic factors.